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Hum. Reprod. Advance Access published online on October 5, 2007
Human Reproduction, doi:10.1093/humrep/dem238
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Endometrial vessel maturation in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time

Ravet Stéphanie1,{dagger}, Soraya Labied1,{dagger}, Silvia Blacher1, Francis Frankenne1, Carine Munaut1, Viviana Fridman2, Aude Beliard1, Jean-Michel Foidart1,3,{dagger} and Michelle Nisolle1,3,4,{dagger}

1 Laboratory of Tumor and Development Biology, Center of Experimental Cancer Research (CECR), University de Liège, Tour de Pathologie (B23), Avenue de l'hôpital, GIGA-R, Sart-Tilman, B-4000 Liège, Belgium 2 Department of Anatomopathology, Citadelle, University of Liège, B-4000 Liège, Belgium 3 Department of Gynecology, CHU, University of Liège, B-4000 Liège, Belgium

4 Correspondence address. Laboratory of Tumor and Development Biology, Center of Experimental Cancer Research (CECR), University de Liège, Tour de Pathologie (B23), Avenue de l'hôpital, GIGA-R, Sart-Tilman, B-4000 Liège, Belgium. Tel: +32-4-366-25-69; Fax: +32-4-366-29-36; E-mail: michelle.nisolle{at}chu.ulg.ac.be

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS), although inserted to reduce heavy menstruation, causes irregular early transient bleeding. The objective of the study was to document quantitative changes in endometrial vessels of short- (≤3 months) and long-term (≥12 months) LNG users. The area, density and maturation of endometrial vessels were quantified in 19 endometrial biopsies of women with LNG-IUS and in 10 normally ovulating patients during mid-luteal phase.

METHODS: Vessel maturation was evaluated by double immunostaining using anti-von Willebrand factor (endothelial cell marker) and anti-alpha Smooth Muscle Actin (vascular smooth muscle cells) antibodies. Vessel area, number and density were quantified with a novel computer-assisted image analysis system.

RESULTS: Endometrium exposed to LNG-IUS for 1–3 months displayed a 11.5-fold increase in small naked vessel number. The partially mature vessel ({alpha}SMA partially positive) number increased six times. After long-term LNG-IUS treatment, the immature and partially mature vessel number remained four times higher than in the control group. Vessel area and density also increased dramatically in a time-dependent pattern with LNG-IUS use.

CONCLUSIONS: Levonorgestrel affects blood vessel number, area, density and maturation in a time-dependent pattern that may explain the early transient increase in breakthrough bleeding with the LNG-IUS.

Key words: endometrium/levonorgestrel/bleeding/vascularization/image analysis

{dagger} These authors contributed equally.

Submitted on March 12, 2007; resubmitted on May 16, 2007; accepted on June 27, 2007.


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